UMLS:C0026764 - FACTA Search

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Query: UMLS:C0026764 (multiple myeloma)
36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Markers of bone metabolism were measured in 73 newly diagnosed myeloma patients and in age-matched controls. Correlations to bone disease on X-rays and survival were performed. In urine deoxypyridinoline/creatinine (DPD) and in serum carboxyterminal pyridinoline cross-linked telopeptide of type I collagen (ICTP), procollagen type I carboxy-terminal extension peptide (PICP) and osteocalcin were analyzed. The ratios DPD/osteocalcin and ICTP/osteocalcin were calculated. Skeletal X-ray findings were divided into no, limited and extensive bone involvement. DPD and ICTP levels were significantly elevated in patients compared to controls. Levels increased with advancing skeletal involvement. Serum osteocalcin was elevated in patients without visible bone disease. The level decreased with more advanced bone involvement. The finding of significantly elevated osteocalcin and ICTP levels in patients without bone involvement on X-rays indicates that bone markers might reflect bone disease better than X-rays in untreated myeloma patients. Ratios between bone resorption and bone formation markers added no further information on bone disease or survival. Only ICTP had prognostic value with an inverse correlation between serum levels and survival.
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PMID:Evaluation of bone disease in multiple myeloma: a comparison between the resorption markers urinary deoxypyridinoline/creatinine (DPD) and serum ICTP, and an evaluation of the DPD/osteocalcin and ICTP/osteocalcin ratios. 1035 57

Bone involvement is a central feature of multiple myeloma (MM). We investigated whether serum markers of osteoblastic and osteoclastic activity correlate with the presence of bone disease and survival in 313 MM patients enrolled in a phase III trial (E9486). Five markers were measured, including osteocalcin (OC), carboxy-terminal propeptide of type I collagen (PICP), bone alkaline phosphatase (BAP), carboxy-terminal telopeptide of type I collagen (ICTP) and tartrate-resistant acid phosphatase (TRAP). We analysed the relationship between serum levels of these markers and the presence of bone manifestations, and survival. Serum levels of ICTP and BAP correlated significantly with bone pain, lesions and fractures. Serum level of ICTP was also higher in stage II-III compared with stage I disease. The serum level of ICTP was significantly associated with shortened survival in the univariate analysis. The median survival times were 4.1 and 3.5 years for low and high ICTP respectively (P = 0.02). There was a strong relationship between ICTP and beta-2-micrgolobulin (B2M). ICTP stands out as a significant marker of bone disease. Incorporation of these markers into clinical trials assessing the use of bisphosphonates in MM is needed to determine whether they might serve as indicators of effectiveness of these agents.
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PMID:Prognostic value of serum markers of bone metabolism in untreated multiple myeloma patients. 1084 78

In spite of their adverse side effects, natural and synthetic glucocorticoids (GCs) occupy a unique role in several fields of medicine. They are potent regulators of bone cell growth and differentiation and the actions on the skeleton and related tissues depend on several factors including the dose, duration of the exposure, the steroid type and the species. In humans some of the effects are indirect, such as the regulation of intestinal calcium absorption and PTH secretion. Other effects are due to the cellular response that occurs within the bone microenvironment. It has been well established in in vitro studies that GCs can promote osteoblast differentiation from mesenchymal osteoprogenitors both in rat calvarial culture and in adherent marrow stromal cells. Moreover, GCs are able to enhance expression of the mature osteoblast phenotype, increasing mineralized nodules, osteocalcin secretion, and the bone morphogenetic protein-6 message level. However, the mechanisms by which GCs affect bone metabolism are still unclear. Recent studies with GCs on bone cells suggested that the production of cytokines and growth factors and the expression of their receptors may also be influenced by GCs. In fact, GCs are able to inhibit the synthesis of cytokines, such as interleukin-1 which stimulates bone remodeling by monocytes and macrophages. Moreover, osteoprotegerin, a recently cloned member of the tumor necrosis factor receptor family, is down-regulated by GCs, offering a possible interpretation for the induction of bone resorption by GCs. GC-induced inhibition of bone resorbing cytokines may contribute to explain the therapeutic actions of GCs in several diseases such as rheumatoid arthritis and myeloma. Furthermore, GCs modulate osteoclast recruitment, even if there is no clear explanation for a direct effect of GCs on osteoclastic precursors. Sustained stimulation of matrix degradation by isolated avian osteoclasts incubated with GCs has been reported, as well as cytotoxic effects on osteoclastic cells from neonatal rat long bones.
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PMID:Corticosteroid-induced osteoporosis: pathogenesis and prevention. 1094 68

In order to evaluate the use of recently developed assays of bone metabolism in multiple myeloma we performed a histomorphometric study of bone biopsies in 16 myeloma patients. Furthermore, we measured the levels of interleukin-6 (IL-6), soluble IL-6 receptor (IL-6sR), IL-1beta, tumour necrosis factor (TNF) alpha, TNFbeta, and transforming growth factor (TGF) beta in marrow plasma aspirated from the biopsy area. MARKERS OF BONE RESORPTION: The N-terminal telopeptide of collagen I (Ntx) in urine showed a strong positive correlation with the dynamic histomorphometric indices of bone resorption (r=0.68-0.72). Slightly weaker correlations were observed between the dynamic indices of bone resorption and the C-terminal telopeptide of collagen I (ICTP) in serum (r= 0.57-0.62) and deoxypyridinoline (Dpyr) in urine (r= 0.54), whereas urinary pyridinoline (Pyr) did not correlate with the histomorphometric findings. MARKERS OF BONE FORMATION: Serum C-terminal propeptide of procollagen I (PICP) and serum bone-specific alkaline phosphatase (bAP) showed significant correlations with the dynamic parameters of bone formation (r=0.57-0.58), whereas serum osteocalcin and serum total AP did not. CYTOKINES: Highly significant correlations were observed between marrow IL-6 and rates of bone resorption and activation frequency (r=0.76-0.82) and with serum ICTP (r=0.63). Minor, but also significant correlations were observed between the resorptive indices and IL-6sR and IL-1beta. The data indicate that measurements of the biochemical markers of bone metabolism may be useful in monitoring myeloma bone disease, and might thus be of use for dose titration of bisphosphonate therapy.
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PMID:Biochemical markers of bone metabolism reflect osteoclastic and osteoblastic activity in multiple myeloma. 1099 32

To test the potential of immunoreactive BSP, a non-collagenous bone matrix component, as a clinical guide in patients with plasma cell dyscrasias, serum BSP concentrations were measured in 62 patients with newly diagnosed multiple myeloma (MM) followed over a period of 4 years, in 46 patients with monoclonal gammopathy of undetermined significance (MGUS), in 71 patients with untreated benign vertebral osteoporosis (OPO), and in 139 healthy adults. Results were compared with clinical and laboratory data, including serum osteocalcin (OC), and urinary pyridinoline (PYD) and deoxypyridinoline (DPD) as markers of bone turnover. In MM, serum BSP, and urinary PYD and DPD were higher than in healthy controls and in MGUS or OPO (P< 0.001). BSP levels correlated with the bone marrow plasma cell content (r = 0.40, P< 0.001), and serum beta2-microglobulin (r = 0.31, P < 0.01). The differentiation of MM from healthy controls and from MGUS or OPO was highest for BSP. After chemotherapy, BSP reflected the response to treatment and correlated with the change in monoclonal protein (r = 0.55, P< 0.001). MM patients with normal baseline BSP levels survived longer than patients with initially elevated BSP values (P< 0.001, log rank test). Only serum monoclonal protein and BSP were independent predictors of survival. We conclude that in MM, BSP levels are associated with skeletal involvement and tumour cell burden. The quantification of serum BSP may be a non-invasive method for the diagnosis and follow-up, and may improve the prognostic value of conventional staging in MM.
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PMID:Serum bone sialoprotein as a marker of tumour burden and neoplastic bone involvement and as a prognostic factor in multiple myeloma. 1116 99

Bisphosphonates are potent inhibitors of osteoclastic activity and reduce the disease-related skeletal complications when they are used in combination with chemotherapy in patients with multiple myeloma (MM). Pamidronate also inhibits apoptosis of primary osteoblastic cells and probably induces apoptosis on human MM cells and osteoclasts. It has been reported that interferon-alpha (IFN-alpha) decreases bone resorption and that low doses of IFN-alpha result in a significant increase in serum osteocalcin (OSC). The aim of this study was to determine the effects of pamidronate treatment on biochemical markers of bone resorption [cross-linked N-telopeptides of type I collagen (NTx)], bone formation [bone alkaline phosphatase (BAP) and OSC], disease activity [beta2-microglobulin, CRP, paraprotein], and interleukin-6 (IL-6) in patients with MM in plateau phase under IFN-alpha maintenance. The above parameters were evaluated in 28 patients (13 M, 15 F, median age 70 years) during maintenance treatment, before the addition of pamidronate and after 1, 3, 6, 9, 12, and 14 months of the combined therapy. The addition of pamidronate to maintenance treatment resulted in a significant reduction of NTx, IL-6, beta2-microglobulin, CRP from the 3rd month and paraprotein from the 6th month of treatment, whereas BAP and OSC were significantly increased from the 6th month. These changes continued during the 14-month follow-up of the combined treatment. Multivariate analysis showed a significant negative correlation between changes of BAP and OSC and the patients' age. The greater increase of the bone formation markers was observed in younger patients. These results suggest that, in addition to the inhibition of osteoclastic activity, pamidronate in combination with IFN-alpha was shown to induce bone formation in patients with MM in the plateau phase.
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PMID:Pamidronate increases markers of bone formation in patients with multiple myeloma in plateau phase under interferon-alpha treatment. 1168 35

Technetium 99m-2-methoxyisobutil-isonitrile (Tc-99m-MIBI), also called sestaMIBI, has been used successfully to detect malignant tumours at diagnosis. Recently, it has been proposed as a safe and effective tracer in patients with multiple myeloma (MM). The purpose of this study was to demonstrate the value of the Tc-99m-MIBI uptake in disease detection and to assess the correlation between the uptake of this scintigraphy agent and prognostic factors in newly diagnosed MM patients. Thirty-five untreated patients were enrolled in the study. Tc-99m-MIBI scanning was performed in 33 patients after intravenous injection of 7.4 MBq/kg. Whole-body anterior and posterior scans were obtained after 30 min, 60 min, 2 and 4 h. The correlation between known prognostic factors of MM and the intensity of Tc-99m-MIBI uptake was assessed. Our results showed seven patients with an intensity score of I0, 12 patients with I1, eight patients with I2 and six patients with a score of I3. There was a positive correlation between Tc-99m-MIBI intensity and C-reactive protein (CRP; r=0.506, P < 0.01), erythrocyte sedimentation rate (ESR; r=0.368, P < 0.05), beta2- microglobulin (beta2M; r=0.749, P < 0.001), interleukin-6 (IL-6; r=0.823, P < 0.001), soluble Interleukin-6 receptor (sIL-6r; r=0.806, P < 0.001), serum calcium (r=0.578, P < 0.001) and bone alkaline phosphatase (BAP; r=0.472, P < 0.01). An inverse correlation was found between Tc-99m-MIBI intensity and osteocalcin (OC) and type I procollagen carboxyterminal propeptide (PICP). In conclusion, the results of this study suggest that more extensive disease activity, as determined by high levels of CRP, beta2M, IL-6 and sIL-6r correlated with a higher uptake of the radiotracer.
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PMID:Correlation between the uptake of Tc-99m-sestaMIBI and prognostic factors in patients with multiple myeloma. 1206 79

Myelomatous bone disease affects about 90% patients with multiple myeloma and solitary myeloma as well. In initial stage it is manifested as osteopenia with osteoporosis or osteolytic foci, pathologic fractures followed by neurologic complications. Ethiopathogenitically a role is played by cytokine interactions with local chemokines produced by myeloma cells and activated stromal and hemopoietic cells (osteoblasts, monocytes, macrophages) resp. From the TNF-alpha family glycoprotein complexes are liberated (RANK-L), which support activation and proliferation or are inhibitory (osteoprotegerins). Similarly in the family TGF-beta several izotypes of antiinflammatory cytokines are known (the most important is TGF-beta 1 and the morphogenetic protein-2), which have a fibrotizing effect in bones, because the produced osteoid is insufficiently mineralized. The effect is a pathologic remodelation of the skeleton. In the diagnosis of multiple myeloma the immunological knowledge is used in the initial diagnosis (immunophenotypization, follow up of TNF-alpha, TGF-beta 1, IL-1, IL-6 etc). Important are also biochemistry values of increased osteoresorption (changes of calcium, parathormone, excretion of collagen fission products, osteocalcin, the bone alkaline phosphatase). In the following part the authors inform about favourable results of long-term treatment with bisphosphonates (Bonefos, Ibandronate) in combination with anti-tumor chemotherapy in 364 patients. During a 15 years observation period median survival of 94 months with a 35% probability of 10 year survival was achieved with a significant decrease of bone complications in 58% compared to 14% in the placebo group.
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PMID:[Bone changes in multiple myeloma--current etiopathogenic, diagnostic and therapeutic aspects]. 1219 8

Hepatocyte growth factor (HGF) has been shown to be involved in angiogenesis, epithelial cell proliferation, and osteoclast activation. HGF and its receptor are expressed on myeloma cell lines and could be involved in the pathogenesis of bone destruction in multiple myeloma (MM). The aim of this study was to examine serum levels of HGF in untreated MM patients and its correlation with bone turnover indices and markers of disease activity. Forty-seven newly diagnosed MM patients and 25 controls were included: 12 patients were of stage I, 13 of stage II, and 22 of stage III (Durie-Salmon classification). Bone lesions were scored from 0 to 3, according to X-ray findings. Serum osteocalcin (OC), interleukin-6 (IL-6), TNF-alpha, beta(2)-microglobulin (beta(2)M), CRP, calcium, and 24-hr urine N-telopeptide cross-links of collagen breakdown (NTx) were determined. HGF levels were significantly higher at stage III compared to stages II and I (medians: 1,990.4 vs. 1,743.8 and 1,432.4 pg/mL, respectively, P < 0.05). Similarly, NTx, IL-6, TNF-alpha, CRP, beta(2)M, and calcium increased significantly with advancing stage (P < 0.01). OC was higher at stage I in comparison to stages II and III (P < 0.01). All parameters were significantly higher in patients than controls. HGF showed a strong correlation with IL-6 and TNF-alpha and less with beta(2)M, CRP, NTx, and OC. We conclude that serum HGF levels are increased in advanced stages of MM disease and extended bone lesions. HGF correlates with IL-6 and TNF-alpha, which are cytokines involved in osteoclast stimulation in MM. However, an independent association of HGF with bone turnover markers was not shown in this study, thus its role in MM bone disease needs to be further clarified.
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PMID:Elevated serum concentration of hepatocyte growth factor in patients with multiple myeloma: correlation with markers of disease activity. 1266 32

Tartrate-resistant acid phosphatase isoform-5b (TRACP-5b), a new marker reflecting osteoclast activity, and osteoprotegerin (OPG) were measured in 121 patients with multiple myeloma (MM) at diagnosis, and in 63 of them during pamidronate administration, to define their correlation with the extent of bone disease and disease activity in MM. Radiographic evaluation of the skeleton, measurement of other markers of bone remodelling, including N-terminal cross-linking telopeptide of type-I collagen (NTX), bone alkaline phosphatase and osteocalcin and of markers of disease activity (beta2-microglobulin, paraprotein, interleukin-6 (IL-6), were also performed. Levels of TRACP-5b were increased (p <.0001), while OPG was decreased in MM patients compared to controls (p <.01). TRACP-5b levels were associated with the radiographically assessed severity of bone disease (p <.0001) as well as with levels of NTX, IL-6 and beta2-microglobulin (p <.001, for each biochemical parameter, respectively). The combination of pamidronate with VAD-chemotherapy produced a reduction in TRACP-5b, NTX, IL-6, paraprotein and beta2-microglobulin levels from the 2nd month of treatment, with no effect on bone formation and OPG. A strong correlation was observed between changes in TRACP-5b and changes in NTX, IL-6 and beta2-microglobulin, while TRACP-5b predicted the disease progression in 5 patients. These findings suggest that TRACP-5b is increased in MM, reflects the extent of myeloma bone disease and may have a predictive value. TRACP-5b has also proved to be very useful for monitoring antimyeloma treatment, which had no effect on OPG levels.
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PMID:Tartrate-resistant acid phosphatase isoform 5b: a novel serum marker for monitoring bone disease in multiple myeloma. 1284 88

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